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Impact of creatine supplementation alone or combined with exercise on inflammatory and clinical outcomes in chronic musculoskeletal pain treated in the rheumatological field: a systematic review.

Creatine supplementation has demonstrated ergogenic and anabolic effects in healthy and clinical populations. However, its potential therapeutic role in individuals with chronic musculoskeletal pain treated in rheumatological contexts remains unclear. The aim was to evaluate the efficacy and safety of creatine supplementation on pain, physical function/disability, quality of life, muscle strength, skeletal muscle mass, and inflammatory markers in people with chronic musculoskeletal pain usually treated from the rheumatological field. A systematic review was conducted following PRISMA guidelines. Searches were performed in MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE up to July 2026. Eligible studies were randomized or nonrandomized clinical trials that provided creatine supplementation alone or in combination with exercise as a treatment compared to a control or placebo group. Eight studies (n = 189) were included, encompassing fibromyalgia, osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis. Creatine dosages varied from chronic low-dose to loading protocols (20 g/d, 2-5 g/d). Combined creatine plus resistance training may improve strength, skeletal muscle mass, and quality of life beyond exercise alone in osteoarthritis. Trials on fibromyalgia suggest an increase in muscle strength, but inconsistent effects on pain. Rheumatoid arthritis studies suggest gains in skeletal muscle mass and, in pilot studies, reduced disease activity. No major adverse events were reported. In conclusion, creatine supplementation alone may be insufficient to obtain clinical benefits, while combined with resistance exercise it could offer potential benefits for muscle strength, skeletal muscle mass and certain aspects of quality of life in these clinical conditions. However, evidence on pain and inflammation remains limited; Furthermore, the response across different clinical conditions is heterogeneous, highlighting the need for larger, high-quality trials.

Humans

Could creatine supplementation combined with physical rehabilitation accelerate return to play in athletes with patellar tendinopathy?

BACKGROUND: Several dietary supplements have been proposed to positively influence the rehabilitation process following injury. However, to date, no studies have specifically examined the effects of scientifically supported ergogenic aids on recovery outcomes when combined with physical performance interventions. Therefore, the aim of this study was to analyze the ergogenic effects of creatine supplementation on neuromuscular performance, tendon thickness, pain, and body composition in athletes diagnosed with patellar tendinopathy (PT). METHODS: Using a triple-blind experimental design, 20 federated athletes (age: 33.7&#x2009;&#xb1;&#x2009;9.84 years) with PT were randomly assigned to either a creatine supplementation group (CR; n&#x2009;=&#x2009;9) or a placebo group (PLA; n&#x2009;=&#x2009;11). All participants followed a physical rehabilitation intervention that included daily eccentric training combined with stretching exercises, along with one session every 10 days of extracorporeal shock wave therapy (ESWT) and manual therapy targeting the tendon and surrounding muscle tissue. At the end of each eccentric training session, the participants ingested 3 capsules of creatine monohydrate - Creapure&#xae; (CR) or sucrose (PLA). At the beginning (PRE), after 4 weeks (MID), and after 8 weeks (POST), the pain level (Victorian Institute for Sports Assessment-Patella, VISA-P), tendon thickness (echography), body composition (bioelectrical impedance system), and neuromuscular performance using a countermovement jump test (CMJ) and a strength test (5-RM) of knee extension in the injured leg. RESULTS: A significant main effect of time was observed for VISA-P scores (p&#x2009;<&#x2009;0.001; &#x3b7;2 p&#x2009;=&#x2009;0.626), indicating a reduction in pain over time in both the creatine (CR) and placebo (PLA) groups. At POST, both groups showed significant improvements compared to PRE (CR: 78.0 points [69.2-86.8] vs. 60.6 points [53.4-67.7]; p&#x2009;=&#x2009;0.002; PLA: 75.2 points [66.3-84.0] vs. 60.0 points [52.5-67.5]; p&#x2009;=&#x2009;0.003). However, only the CR group showed a statistically significant improvement in the MID compared to PRE (MID: 70.2 points [60.0-80.5]; p&#x2009;=&#x2009;0.027). A significant main effect of time was observed for both tendon thickness (p&#x2009;<&#x2009;0.001; &#x3b7;2 p&#x2009;=&#x2009;0.629) and the 5-RM leg extension test (p&#x2009;<&#x2009;0.001; &#x3b7;2 p&#x2009;=&#x2009;0.739), with both groups showing progressive improvements over time. Nevertheless, as trend toward a statistically significant time&#xb7;supplementation interaction was observed (p&#x2009;=&#x2009;0.099; &#x3b7;2p&#x2009;=&#x2009;0.126), with an increase in performance only in CMJ in MID vs PRE (36.8&#x2009; cm (33.8-39.7) vs 34.3&#x2009; cm (30.8-37.7); p&#x2009;=&#x2009;0.019) and POST vs MID (POST: 37.6&#x2009; cm (33.5-41.8); p&#x2009;=&#x2009;0.015). CONCLUSIONS: A physical rehabilitation program involving eccentric training, stretching, and ESWT is effective in reducing tendon thickness and increasing muscle strength. However. It seems that the addition of CR induces an earlier reduction of pain and a positive effect on CMJ performance. Therefore, CR could be considered as an ergogenic recovery aid in athletes with PT.

Humans

Effects of six weeks of guanidinoacetic acid supplementation with and without creatine monohydrate on cognitive function and markers of health in healthy adults.

BACKGROUND: Guanidinoacetic acid (GAA) supplementation has been reported to increase brain creatine content more effectively than creatine monohydrate (CrM). However, the effects on cognitive function are unclear. PURPOSE: The purpose of this proof-of-concept exploratory clinical trial was to determine whether GAA supplementation with and without CrM affects cognitive function and/or markers of health. METHODS: In a double-blind, randomized, and counterbalanced manner, 58 healthy and active adults (33 females, 35.5&#x2009;&#xb1;&#x2009;14 years, 76.2&#x2009;&#xb1;&#x2009;14 kg) ingested a PLA (PLA, 2 &#xd7; 6 g/d maltodextrin), GAA (2 &#xd7; 1 g/d)&#x2009;+&#x2009;PLA (2 &#xd7; 5 g/d), or GAA (2 &#xd7; 1 g/d)&#x2009;+&#x2009;CrM (2 &#xd7; 5 g/d) for six weeks. The participants donated fasting blood samples and completed a battery of tests and questionnaires assessing various aspects of function, mood, stress, sleep quality, and markers of health at baseline and after six weeks of supplementation. Data were analyzed using General Linear Model (GLM) multivariate and univariate with repeated measures, and mean changes from baseline with 95% confidence intervals, and Chi-squared analysis, and considered significant when the probability of error was 0.05 or less, and approaching significance (p&#x2009;>&#x2009;0.05-p&#x2009;<&#x2009;0.10). RESULTS: GAA supplementation tended to improve overall reaction time (-241.8&#x2009;ms [-533, 50], p&#x2009;=&#x2009;0.10) while significant interaction effects were observed in overall reaction time (p&#x2009;=&#x2009;0.031-330 ms [-629, -31]) and YES reaction time (-290&#x2009;ms [-484, -96], p&#x2009;=&#x2009;0.004) while recalled correct reaction time (-178&#x2009;ms [-374, 21], p&#x2009;=&#x2009;0.078) and recalled correct YES (7.4 % [-1, 15.8], p&#x2009;=&#x2009;0.084) approached significance compared to PLA. Limited to no effects were observed on the Delayed Picture Recognition Task Test, Digit Vigilance Task Test, Corsi Block Task Test, or Stroop Color-Word Task Test. The amount of time engaged in moderate physical activity was significantly greater (p&#x2009;<&#x2009;0.05) in the GAA group compared to PLA. Participants in the GAA group reported a lower frequency of controlling irritations (p&#x2009;=&#x2009;0.036), and feeling like difficulties are mounting (p&#x2009;=&#x2009;0.053) on the Perceived Stress Scale. Some positive and potentially undesirable effects were observed in sleep quality assessments. The quality of life assessment revealed that participants in the GAA group reported less frequent feelings of being worn out (p&#x2009;=&#x2009;0.068) and that their health was excellent (p&#x2009;=&#x2009;0.092) while those in the GAA&#x2009;+&#x2009;CrM group reported more frequent limitations when bending, kneeling, or stooping (p&#x2009;=&#x2009;0.053), more often feeling full of life (p&#x2009;=&#x2009;0.081), and less frequency in feeling downhearted and depressed (p&#x2009;=&#x2009;0.066). No clinically meaningful changes were observed in blood markers or self-reported side effects among the groups. CONCLUSION: Dietary supplementation with GAA (2 g/d) and the combination of CrM (10 g/d&#x2009;+&#x2009;GAA 2 g/d) for six weeks improved delayed verbal episodic recognition memory and retrieval speed and some measures of perceived stress, sleep quality, and quality of life. However, most cognitive tests were not affected, particularly when comparing the GAA to the PLA group; there were some inconsistencies in the findings, and several differences only approached significance. Additional research is needed before conclusions can be drawn. Clinical trial registration: ISRCTN68542582.

Humans

Creatine formulations and repeated sprint training: effects on physical and physiological adaptations in soccer players during the short-term preparation phase.

BACKGROUND: This research examined the impact of various creatine (Cr) supplementation formulations during a 4-week preparatory phase on the efficacy of repeated sprint training (RST) and on improvements in physical and physiological performance in male soccer athletes. METHODS: A total of forty collegiate young soccer players volunteered for the study. They were randomly divided into four groups: creatine monohydrate (Cr-Mon, n&#x2009;=&#x2009;10), creatine ethyl ester (Cr-Ee, n&#x2009;=&#x2009;10), creatine hydrochloride (Cr-Hcl, n&#x2009;=&#x2009;10), and placebo (PL, n&#x2009;=&#x2009;10). All athletes engaged in a 4-week training intervention, three times a week (i.e. 12 sessions), and physical (countermovement vertical jump [CMVJ], 20-m sprint, and L-run) and physiological (Wingate anaerobic power and incremental exercise tests) performance were assessed both before and after the training period. RESULTS: All training groups improved physical and physiological performance following the 4-week intervention period (p&#x2009;<&#x2009;0.05). Additionally, the groups receiving the Cr supplement exhibited significantly greater changes (p&#x2009;=&#x2009;0.001) in physical performance, peak power output, and fatigue index compared to the PL group. However, no significant differences were found among the groups regarding mean power output and VO2max. Notably, the Ee and Hcl forms of Cr showed superior gains (p&#x2009;<&#x2009;0.05) in physical performance and peak power compared to the Mon form after the 4-week intervention. CONCLUSIONS: The results underscore the importance of Cr ingestion in enhancing adaptations for short-term physical performance tasks, highlighting the effectiveness of the Ee and Hcl forms in further improving the CMVJ, 20-m sprint, L-run, and peak power among soccer players during the short-term preparation phase.

Humans

Activation of pyruvate dehydrogenase in adipose tissue by insulin. Evidence for an effect of insulin on pyruvate dehydrogenase phosphate phosphatase.

1. The mechanism by which insulin activates pyruvate dehydrogenase in rat epididymal adipose tissue was further investigated. 2. When crude extracts, prepared from tissue segments previously exposed to insulin (2m-i.u/ml) for 2min, were supplemented with Mg-2+, Ca-2+, glucose and hexokinase and incubated at 30 degrees C, they displayed an enhanced rate of increase in pyruvate dehydrogenase activity compared with control extracts. 3. When similar extracts were instead supplemented with fluoride, ADP, creatine phosphate and creatine kinase, the rate of decrease in pyruvate dehydrogenase activity observed during incubation at 30 degrees C was unaffected by insulin treatment. 4. It is suggested that insulin increases the fraction of pyruvate dehydrogenase present in the tissue in the active dephospho form by increasing the activity of pyruvate dehydrogenase phosphate phosphatase.

Adenosine Diphosphate

A method for investigating the role of calcium in the shape change, aggregation and serotonin release of rat platelets.

1. Effects of the platelet secretagogues thrombin and Concanavalin A (Con A) on shape change and release have been studied under conditions where external Ca2+ and ADP have been controlled. 2. In the absence of detectable aggregation both Con A- and thrombin-induced release of serotonin are markedly dependent upon extracellular calcium. 3. Con A, unlike thrombin, does not produce aggregation in calcium-supplemented medium. 4. The above property of Con A suggests that, in combination with added creatine phosphate and creatine phosphokinase, this ligand will be of value in the analysis of calcium-dependent release in platelets.

Animals

Polybrominated biphenyl (PBB) in the growing pig diet.

Twelve pigs which averaged 13.7 kg were randomly allotted from litters to a corn-soybean meal grower diet containing 0, 20, or 200 ppm of polybrominated biphenyls (PPB). During a 16-week growth trial, average daily gain (kg), average daily feed (kg) and feed/gain for pigs on diets containing 0, 20, or 200 ppm of PBB, respectively, were 0.82, 2.45, 2.99; 0.67, 1.88, 2.79; 0.45, 1.23, 2.70. Mean daily gain differences between all lots were highly significant (p < 0.01). Blood from each pig was withdrawn biweekly through the first 8 weeks of the trial and at 4 week intervals thereafter. Hemoglobin and hematocrit differed significantly only at the 6 weeks bleeding, being reduced in pigs receiving 200 ppm of PBB. Erythrocyte reduced glutathione concentration and glutathione peroxidase activity were not significantly influenced by level of dietary PBB. Serum lactic dehydrogenase activity was significantly higher in control pigs than in either PBB supplemented lots at 16 weeks. There was no significant influence of PBB upon serum glutamic oxaloacetic transaminase, serum alkaline phosphatase or serum creatine phosphokinase. Based on these enzyme assays, PBB produced no evidence of significant necrosis of liver, myocardium, or skeletal muscle. There was no consistent effect of dietary PBB upon total serum protein concentration or electrophoretic profile. Pigs on either level of PBB did not have overt clinical signs of toxicity during the 16-week test period with the exception of a dermatosis on the ventral surface of two of the pigs receiving 200 ppm of PBB. There was a marked increase in liver weight of pigs receiving either level of dietary PBB. Heart, kidney, and adrenals of pigs receiving either level of dietary PBB were heavier as a percent of body weight than that of control pigs. Fat retention of PBB and urinary and fecal PBB excretion were significantly affected by dietary PBB level. Grossly, the glandular portion of the stomach appeared somewhat hyperplastic in pigs on 200 ppm of PBB. Two pigs which had received 200 ppm of PBB were placed on the control diet and over the next 14 weeks normal growth rate occurred. One of these pigs was killed and organ weights were normal. The other pig, a gilt, came into estrus. She was bred and conceived. At the end of gestation, four pigs were born. Three survived and grew normally; the one death at birth examined at gross necropsy did not reveal changes in organ size or other tissue alterations.

Animal Feed

A myogenic cell line with altered serum requirements for differentiation.

Dfferentiation properties of a cell line, L84, which originated from a non-fusing clone isolated from the myogenic line L8, are described. In nutritional medium supplemented with 10% serum used routinely with L8 cells, L84 cells continue to proliferate to very high densities and fail to form multinucleated fibres. When grown in medium supplemented with 2% horse serum of 2% horse serum plus 0.1% microng/ml insulin, L84 cells behave very similarly to L8 cells grown in medium supplemented with 10% horse serum: when the cultures reach confluency, proliferation decreases and cells start to fuse and form a dense network of fibres. Large increases in creatine kinase activity and synthesis of myosin are associated with cell fusion. Under conditions in which L84 cells do not fuse the increase in these synthetic activities is not observed, even after extremely high cell densities are reached. The data show that L84 cells retain the programme for their differentiation into muscle fibres. The difference between L84 and its progenitor line L8 lies in the sensitivity to the environmental conditions which trigger the expression of this programme.

Animals

A diagnostic strategy for myocardial infarction.

In attempting to make the diagnosis of myocardial infarction, the family physician has available an increasing array of enzyme and nuclear imaging techniques to add to the clinical and electrocardiographic findings. In this review several of the new diagnostic tests are described, and their role is discussed both in supplementing and replacing older diagnostic tests. A general strategy for employing both old and new tests is proposed, with a goal of achieving both increased diagnostic accuracy and reduced charges for laboratory tests.

Creatine Kinase

Serum alkaline phosphatase activity in relation to liveweight of lambs.

Groups of lambs were fed four levels of a diet based upon oaten grain. Two groups gained weight rapidly, one less rapidly and the other lost liveweight over a 32-day period. Serum alkaline phosphatase activity was found to be closely correlated to liveweight, in a positive linear manner, in those lambs gaining weight rapidly. This relationship was similar in lambs of R or r blood group. Supplementation of the diet with limestone and or sodium chloride did not influence the relationship. This relationship is considered to reflect the influence of the dietary treatments upon the rate of skeletal metabolism.

Alkaline Phosphatase

[Comparative study of nitrogen savings during enteral and parenteral feeding (Trive 1000)].

Through a study of Nitrogen balances, the authors compare the effectiveness of a proteinic intake carried out per os or by intravenous route. The study involved 22 different carcinoma carriers and lasted for 9 days during which the Nitrogen intake was effected either by the digestive tract or by intravenous route supplemented by a sufficient caloric ration. In the latter case, the aminoacid intake was supplied by Trive 1000 combined with glucides and lipids which were then quantitatively deducted from the enteral intake. A study of the results showed that the assimilation of the Nitrogen injected intravenously was very similar to the one obtained by enteral route.

Adult

Calcium: bivalent cation in the bivalent psychoses.

Decreases in cerebrospinal fluid (CSF) calcium accompany mood elevation and motor activation in depressed patients undergoing treatment with ECT, lithium, and total sleep deprivation. Similarly, decreases in CSF calcium occur during acute psychotic agitation or mania. On the other hand, periodic recurrences of such agitated states are accompanied at their onset by transient increases in serum calcium and phosphorus. Several observations suggest that such serum ion shifts may trigger the more enduring and opposite shifts in CSF calcium and, in turn, the manic behavior. Progressive restriction of dietary calcium was earlier reported to mitigate and finally abolish both rhythmic rises in serum calcium and periodic agitated episodes in one psychotic patient. Lithium, which decreases the efficiency of alimentary calcium absorption, may function similarly. Conversely, a modest oral calcium lactate supplement (approximately one additional Recommended Daily Allowance of dietary calcium) seemed to slightly intensify agitation in six patients. Dihydrotachysterol (DHT), an analogue of vitamin D, which more exactly mimics the increase in both serum calcium and phosphorus, appeared in at least one periodically psychotic patient to trigger and opposite shift in CSF calcium. Moreover, in eight patients, manic symptomatology appeared de novo or grew significantly and substantially worse during 2 to 6 weeks of oral DHT administration. On the other hand, in 12 patients, subcutaneous injections of synthetic salmon calcitonin (SCT) decreased serum calcium and phosphorus, increased CSF calcium, and decreased agitation while augmenting depressive symptomatology. SCT also decreased quantified motor activity, frequency and severity of periodic agitated episodes, serum CPK and prolactin, and nocturnal sleep, while DHT or calcium lactate had opposite effects on the same parameters.

Animals